IT-TIMI 22). As a drug target CYP17A1 inhibitors Currently, the FDA has approved only one CYP17A1 inhibitor, abiraterone, which contains a steroidal scaffold that is similar to the endogenous CYP17A1 substrates. Abiraterone is structurally similar to the substrates of other cytochrome P450 enzymes involved in steroidogenesis, and interference can pose a liability in terms of side effects. Using nonsteroidal scaffolds is expected to enable the design of compounds that interact more selectively with CYP17A1. Potent inhibitors of the CYP17A1 enzyme provide a last line defense against ectopic androgenesis in advanced prostate cancer. The drug abiraterone acetate, which is used to treat castration-resistant prostate cancer, blocks the biosynthesis of androgens by inhibiting the CYP17A1 enzyme. Abiraterone acetate binds in the active site of the enzyme and coordinates the heme iron through its pyridine nitrogen, mimicking the substrate. Since 2014, galeterone has been in phase III clinical trials for castration-resistant prostate cancer. Ketoconazole is an older CYP17A1 inhibitor that is now little used. However, ketoconazole competitively inhibits CYP17A1, therefore its effectiveness will depend on the concentration of ketoconazole. This is in contrast to the abiraterone acetate, that permanently (rather than competitively) disables CYP17A1, once it binds to it. Seviteronel (VT-464) is a novel CYP17A1 inhibitor which is aimed to avoid co-administration of glucocortoid therapy. In the 2010s it underwent various phases of clinical studies and preclinical models as a drug against prostate cancer or breast cancer. Steroidogenesis Additional images See also Steroidogenic enzyme Cytochrome P450 oxidoreductase deficiency References Further reading External links 17